Adhesion between cells is a feature of all multicellular organisms, including humans. One class of proteins that mediate adhesion between cells is the cadherin family of proteins. Cadherin is a general term that identifies a family of calcium-dependent cell-cell adhesion molecules consisting of several distinct proteins. Typically each cadherin molecule crosses the plasma membrane of a cell so that there is an extracellular portion of the cadherin protein as well as an intracellular portion.
On the outside surface of a cell, the extracellular domain of a cadherin protein interacts with the extracellular domain of a cadherin on the adjacent cell. These extracellular interactions contribute to holding neighboring cells together. Different types of cells, for example nerve cells and intestinal cells, may display different types of cadherin proteins on their surfaces.
On the inside surface of the cell membrane, the cytoplasmic domain of the cadherin protein interacts with a set of proteins called catenins or plaque proteins. The catenins or plaque proteins provide a bridge between the cadherin and the cell's cytoskeleton. In addition to the structural function, catenins may also play a role in signaling the cell. One type of signal may be produced when the extracellular cadherin domain interacts with a partner in an adjacent cell.
When a physician suspects that a patient has a tumor, it is typical for a piece of the affected tissue to be removed surgically and sent to a pathology laboratory for analysis and assessment. Typically, the tissue specimen is fixed in 10% formalin and delivered to the pathology laboratory where it is embedded in paraffin and sliced into sections which are processed for analysis in a number of ways (for example, with various stains as further described herein). The pathologist then examines the stained tissue section using microscopic methods. Distinct features of the cells in the tissue are revealed by these methods. The pathologist then classifies the tumors and assesses the patient diagnosis and prognosis based upon the histological characteristics of the tumor cells. More particularly, using established criteria, the pathologist evaluates what is seen in the sections. Most of the pathologist's information is derived from examination of these tissue sections. The results of the analyses are combined into a pathology report. If the tissue contains cancerous cells, the cancer is described in detail, the type of tumor is identified and its particular characteristics described. The characteristics stated in the report are those observed by the pathologist during the examination of the tissue sections. Depending upon the number and type of analytical procedures performed on the tissue sections, the pathologist will learn to varying extent the details that provide the basis for the diagnosis, for judging the tumor grade, and for predicting the patient prognosis.
The decision concerning how to process the tissue sections depends on common and routine practices in the laboratory, with considerations being given to the history of the sample. For example, it is common practice to stain sections with hematoxylin and eosin. Other types of staining may be called for when the pathologist suspects the tumor may be of a particular type. The decisions of how to process tissue sections are based upon the cumulative knowledge and the aggregate experiences of the pathology community. New processing procedures become routine pathology practice when they have been proven to be informative in diagnosis/prognosis and if they are easily incorporated into the standard operations of a pathology laboratory. Research laboratories, in contrast to clinical laboratories, typically identify new ways to examine tissues and then seek to demonstrate their ability in clinical situations.
Because of the relative subjectivity of the foregoing procedure, researchers and pathologists are constantly searching for more objective makers of tumor diagnosis and prognosis. As a result of those investigations, the number of antibodies that are used as tumor markers has steadily increased. However, pathologists and researchers do not yet have access to a comprehensive set of reagents that may be used as universal markers for the diagnosis and prognostic assessment of tumors.
One of the characteristic features of cancer cells is that, relative to their normal counterparts, their cell adhesion systems are different. One manifestation of their altered cell adhesion properties is that many cancers can become metastatic. Thus, it is of interest to determine the status of cell adhesion molecules in cancer cells.
An object of the present invention is to provide a panel for detecting cadherins, catenins or plaque proteins in tissues. Yet another object of the present invention is to provide a panel of antibodies for detecting cadherins, catenins or plaque proteins in tissues. Another object of the present invention is to provide an antibody-based panel for detecting cadherins, catenins or plaque proteins in tissues to assess tumors. Another object of the present invention is to provide antibodies to cadherins, catenins or plaque proteins and to provide their method of use in the diagnosis and prognosis of human cancers.